Background: HIV and combination antiretroviral therapy (cART) may increase cardiovascular disease (CVD) risk. We assessed the early effects of cART on CVD risk markers in a population with presumed low CVD risk. Methods: Adult patients (n=118) in Lusaka, Zambia were recruited at the time of initiation of cART for HIV/AIDS. Cardiometabolic risk factors were measured before and 90 days after starting cART. Participants were grouped according to cART regimens: Zidovudine + Lamivudine + Nevirapine (n=58); Stavudine + Lamivudine + Nevirapine (n=43); and ‘other’ (Zidovudine + Lamivudine + Efavirenz, Stavudine + Lamivudine + Efavirenz, Tenofovir + Emtricitabine + Efavirenz or Tenofovir + Emtricitabine + Nevirapine, n=17). ANOVA was used to test whether changes in cardiometabolic risk markers varied by cART regimen. Results: From baseline to 90 days after initiation of cART, the prevalence of low levels of high-density lipoprotein cholesterol (<1.04 mmol/L for men and <1.30 mmol/L for women) significantly decreased (78.8% vs. 34.8%, P<0.001) while elevated total cholesterol (TC ≥5.18 mmol/L, 5.1% vs. 11.9%, P=0.03) and the homeostasis model assessment of insulin resistance ≥3.0 (1.7% vs. 17.0%, P<0.001) significantly increased. The prevalence of TC:HDL-c ratio ≥5.0 significantly decreased (44.9% vs. 6.8%, P<0.001). These changes in cardiometabolic risk markers were independent of the cART regimen. Conclusion: Our results suggest that short-term cART is associated with a cardioprotective lipid profile in Zambia and a tendency towards insulin resistance regardless of the cART regimen.